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Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outl ....Understanding the critical processes that control cell death and using this knowledge to kill cells that have evaded death. Cell death is essential for protecting the body against cancer, and defects in cell death pathways contribute to cancer progression. To design new and better cancer therapies we must understand the critical processes which control cell death, and develop effective ways to either reset, or bypass, defects in cell death pathways that contribute to cancer. The program as outlined will elucidate the process of mitochondrial outer membrane permeabilization, a critical event in cell death by apoptosis, and determine how to kill cells in which this event is blocked.Read moreRead less
The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This ....The cell wall substrate delivery mechanisms in plants. This project aims to study the delivery of substrates plants need to biosynthesise sugar polymers. Sugar polymers play key structural and functional roles in plant development and determine quality for all plant-based products including food, textile fibres, building materials and renewable biomass. However, unknown mechanisms regulate and control the transport mechanisms that deliver the building blocks for polysaccharide biosynthesis. This project is expected to increase understanding of nucleotide sugar transport and develop and enhance the biological toolbox for applications involving modelling and engineering of plants, synthesis of industrial biopolymers and production of functional foods.Read moreRead less
Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods ....Multi-functional probes for global analysis of proteome stress in cells. This project aims to create a suite of multi-functional chemical probes to identify damaged proteins that undergo unfolding or specific modifications in cells under stress. These probes will not only generate fluorescence responses to reflect on protein quality control capacity but allow associated proteins and their networks to be identified in complex cellular environments, which is difficult to achieve by current methods. The expected outcome is to deliver new methodology for a comprehensive understanding of the correlation between quality control machinery, stress responses and cell functions. This should provide significant benefits, including contributing to fundamental knowledge on the molecular causes of neurodegenerative diseases.Read moreRead less
New models of mitochondrial fatty acid oxidation disorders. Mitochondrial disease can affect both children and adults and is often fatal. This project will study mitochondrial function in cell types of the heart and brain to better understand how they generate energy in these tissues. This will provide new insights into mitochondrial metabolism and how defects in this process cause mitochondrial disease.
Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which fu ....Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis. Sedentary lifestyles and consumption of high energy foods have led to dramatic increases in the incidence of obesity-related metabolic diseases such as type 2 diabetes and cardiovascular disease, placing enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK), which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Building on recent breakthroughs made at St. Vincent's Institute, this project will produce innovative research into novel mechanisms that control AMPK. These discoveries will greatly increase our understanding of AMPK regulation by cellular processes, and aid the design of more effective AMPK drugs.Read moreRead less
How do nutrient-regulated changes in mitochondrial protein acetylation and sirtuin activity affect mitochondrial function and insulin action? Lysine acetylation affects the function of many proteins. This project will examine how excess nutrient availability and altered sirtuin activity affects the acetylation state and function of mitochondrial proteins. This information may identify therapeutic targets to treat diseases associated with mitochondrial dysfunction.
The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel com ....The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel compounds and strategies for treating obesity. The proposed study will also benefit Australian agriculture and energy industry by providing strategies to improve the production of plant oil and biodiesel. Read moreRead less
The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle ma ....The regulation of skeletal muscle mass. This project aims to delineate a pathway involved in regulating skeletal muscle mass, and examine whether disrupting mitochondrial phospholipid synthesis affects mitochondrial structure and function, causing muscle wasting. Defining a new atrophy pathway will advance understanding of the mechanisms that control muscle mass. This project could have important economic and quality of life benefits, especially for agriculture, where achieving optimal muscle mass ensures international competitiveness, productivity and economic growth, and successful ageing, where maintaining muscle mass is essential.Read moreRead less
Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking ....Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.Read moreRead less
Metabolic control of organ growth and regeneration. One of the fundamental questions in biology is to understand how organ size is regulated at the cellular and organismal level. The Hippo/Yap pathway plays a central role in the regulation of organ size and it is impacted by environmental cues including nutrient status. This research proposal aims to use zebrafish to elucidate the role that the Hippo/Yap pathway plays in reprogramming lipid metabolism to fuel tissue growth in development and reg ....Metabolic control of organ growth and regeneration. One of the fundamental questions in biology is to understand how organ size is regulated at the cellular and organismal level. The Hippo/Yap pathway plays a central role in the regulation of organ size and it is impacted by environmental cues including nutrient status. This research proposal aims to use zebrafish to elucidate the role that the Hippo/Yap pathway plays in reprogramming lipid metabolism to fuel tissue growth in development and regeneration. Ultimately, this work aims to identify metabolic dependencies required for organ growth and regeneration. Expected outcomes include scholarly publications revealing fundamental principles underlying tissue growth, new resources for the research community and training for research students.Read moreRead less